Applicability of an unsupervised cluster model developed on first wave COVID-19 patients in second/third wave critically ill patients.

OBJECTIVE: To validate the unsupervised cluster model (USCM) developed during the first pandemic wave in a cohort of critically ill patients from the second and third pandemic waves. DESIGN: Observational, retrospective, multicentre study. SETTING: Intensive Care Unit (ICU). PATIENTS: Adult patients admitted with COVID-19 and respiratory failure during the second and third pandemic waves. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Collected data included demographic and clinical characteristics, comorbidities, laboratory tests and ICU outcomes. To validate our original USCM, we assigned a phenotype to each patient of the validation cohort. The performance of the classification was determined by Silhouette coefficient (SC) and general linear modelling. In a post-hoc analysis we developed and validated a USCM specific to the validation set. The model's performance was measured using accuracy test and area under curve (AUC) ROC. RESULTS: A total of 2330 patients (mean age 63 [53-82] years, 1643 (70.5%) male, median APACHE II score (12 [9-16]) and SOFA score (4 [3-6]) were included. The ICU mortality was 27.2%. The USCM classified patients into 3 clinical phenotypes: A (n = 1206 patients, 51.8%); B (n = 618 patients, 26.5%), and C (n = 506 patients, 21.7%). The characteristics of patients within each phenotype were significantly different from the original population. The SC was -0.007 and the inclusion of phenotype classification in a regression model did not improve the model performance (0.79 and 0.78 ROC for original and validation model). The post-hoc model performed better than the validation model (SC -0.08). CONCLUSION: Models developed using machine learning techniques during the first pandemic wave cannot be applied with adequate performance to patients admitted in subsequent waves without prior validation.

Assessing the impact of real-time random safety audits through full propensity score matching on reliable data from the clinical information system.

BACKGROUND: Evidence-based care processes are not always applied at the bedside in critically ill patients. Numerous studies have assessed the impact of checklists and related strategies on the process of care and patient outcomes. We aimed to evaluate the effects of real-time random safety audits on process-of-care and outcome variables in critical care patients. METHODS: This prospective study used data from the clinical information system to evaluate the impact of real-time random safety audits targeting 32 safety measures in two intensive care units during a 9-month period. We compared endpoints between patients attended with safety audits and those not attended with safety audits. The primary endpoint was mortality, measured by Cox hazard regression after full propensity-score matching. Secondary endpoints were the impact on adherence to process-of-care measures and on quality indicators. RESULTS: We included 871 patients; 228 of these were attended in ≥ 1 real-time random safety audits. Safety audits were carried out on 390 patient-days; most improvements in the process of care were observed in safety measures related to mechanical ventilation, renal function and therapies, nutrition, and clinical information system. Although the group of patients attended in safety audits had more severe disease at ICU admission [APACHE II score 21 (16-27) vs. 20 (15-25), p = 0.023]; included a higher proportion of surgical patients [37.3 % vs. 26.4 %, p = 0.003] and a higher proportion of mechanically ventilated patients [72.8 % vs. 40.3 %, p < 0.001]; averaged more days on mechanical ventilation, central venous catheter, and urinary catheter; and had a longer ICU stay [12.5 (5.5-23.3) vs. 2.9 (1.7-5.9), p < 0.001], ICU mortality did not differ significantly between groups (19.3 % vs. 18.8 % in the group without safety rounds). After full propensity-score matching, Cox hazard regression analysis showed real-time random safety audits were associated with a lower risk of mortality throughout the ICU stay (HR 0.31; 95 %CI 0.20-0.47). CONCLUSIONS: Real-time random safety audits are associated with a reduction in the risk of ICU mortality. Exploiting data from the clinical information system is useful in assessing the impact of them on the care process, quality indicators, and mortality.

Association of obesity on the outcome of critically ill patients affected by COVID-19.

OBJECTIVE: To evaluate the impact of obesity on ICU mortality. DESIGN: Observational, retrospective, multicentre study. SETTING: Intensive Care Unit (ICU). PATIENTS: Adults patients admitted with COVID-19 and respiratory failure. INTERVENTIONS: None. PRIMARY VARIABLES OF INTEREST: Collected data included demographic and clinical characteristics, comorbidities, laboratory tests and ICU outcomes. Body mass index (BMI) impact on ICU mortality was studied as (1) a continuous variable, (2) a categorical variable obesity/non-obesity, and (3) as categories defined a priori: underweight, normal, overweight, obesity and Class III obesity. The impact of obesity on mortality was assessed by multiple logistic regression and Smooth Restricted cubic (SRC) splines for Cox hazard regression. RESULTS: 5,206 patients were included, 20 patients (0.4%) as underweight, 887(17.0%) as normal, 2390(46%) as overweight, 1672(32.1) as obese and 237(4.5%) as class III obesity. The obesity group patients (n = 1909) were younger (61 vs. 65 years, p < 0.001) and with lower severity scores APACHE II (13 [9-17] vs. 13[10-17, p < 0.01) than non-obese. Overall ICU mortality was 28.5% and not different for obese (28.9%) or non-obese (28.3%, p = 0.65). Only Class III obesity (OR = 2.19, 95%CI 1.44-3.34) was associated with ICU mortality in the multivariate and SRC analysis. CONCLUSIONS: COVID-19 patients with a BMI > 40 are at high risk of poor outcomes in the ICU. An effective vaccination schedule and prolonged social distancing should be recommended.

Clinical and Microbiological Impact of Implementing a Decision Support Algorithm through Microbiologic Rapid Diagnosis in Critically Ill Patients: An Epidemiological Retrospective Pre-/Post-Intervention Study.

BACKGROUND: Data on the benefits of rapid microbiological testing on antimicrobial consumption (AC) and antimicrobial resistance patterns (ARPs) are scarce. We evaluated the impact of a protocol based on rapid techniques on AC and ARP in intensive care (ICU) patients. METHODS: A retrospective pre- (2018) and post-intervention (2019-2021) study was conducted in ICU patients. A rapid diagnostic algorithm was applied starting in 2019 in patients with a lower respiratory tract infection. The incidence of nosocomial infections, ARPs, and AC as DDDs (defined daily doses) were monitored. RESULTS: A total of 3635 patients were included: 987 in the pre-intervention group and 2648 in the post-intervention group. The median age was 60 years, the sample was 64% male, and the average APACHE II and SOFA scores were 19 points and 3 points. The overall ICU mortality was 17.2% without any differences between the groups. An increase in the number of infections was observed in the post-intervention group (44.5% vs. 17.9%, p < 0.01), especially due to an increase in the incidence of ventilator-associated pneumonia (44.6% vs. 25%, p < 0.001). AC decreased from 128.7 DDD in 2018 to 66.0 DDD in 2021 (rate ratio = 0.51). An increase in Pseudomonas aeruginosa susceptibility of 23% for Piperacillin/tazobactam and 31% for Meropenem was observed. CONCLUSION: The implementation of an algorithm based on rapid microbiological diagnostic techniques allowed for a significant reduction in AC and ARPs without affecting the prognosis of critically ill patients.

CARDIAC OUTPUT IN CRITICALLY ILL PATIENTS CAN BE ESTIMATED EASILY AND ACCURATELY USING THE MINUTE DISTANCE OBTAINED BY PULSED-WAVE DOPPLER.

ABSTRACT: Background: Cardiac output (CO) assessment is essential for management of patients with circulatory failure. Among the different techniques used for their assessment, pulsed-wave Doppler cardiac output (PWD-CO) has proven to be an accurate and useful tool. Despite this, assessment of PWD-CO could have some technical difficulties, especially in the measurement of left ventricular outflow tract diameter (LVOTd). The use of a parameter such as minute distance (MD) which avoids LVOTd in the PWD-CO formula could be a simple and useful way to assess the CO in critically ill patients. Therefore, the aim of this study was to evaluate the correlation and agreement between PWD-CO and MD. Methods: A prospective and observational study was conducted over 2 years in a 30-bed intensive care unit (ICU). Adult patients who required CO monitoring were included. Clinical echocardiographic data were collected within the first 24 h and at least once more during the first week of ICU stay. PWD-CO was calculated using the average value of three LVOTd and left ventricular outflow tract velocity-time integral (LVOT-VTI) measurements, and heart rate. Minute distance was obtained from the product of LVOT-VTI × heart rate. Pulsed-wave Doppler cardiac output was correlated with MD using linear regression. Cardiac output was quantified from the MD using the equation defined by linear regression. Bland-Altman analysis was also used to evaluate the level of agreement between CO calculated from MD (MD-CO) and PWD-CO. The percentage error was calculated. Results: A total of 98 patients and 167 CO measurements were analyzed. Sixty-seven (68%) were male, the median age was 66 years (interquartile range [IQR], 53-75 years), and the median Acute Physiology and Chronic Health Evaluation II score was 22 (IQR, 16-26). The most common cause of admission was shock in 81 patients (82.7%). Sixty-nine patients (70.4%) were mechanically ventilated, and 68 (70%) required vasoactive drugs. The median CO was 5.5 L/min (IQR, 4.8-6.6 L/min), and the median MD was 1,850 cm/min (IQR, 1,520-2,160 cm/min). There was a significant correlation between PWD-CO and MD-CO in the general population ( R2 = 0.7; P < 0.05). This correlation improved when left ventricular ejection fraction (LVEF) was less than 60% ( R2 = 0.85, P < 0.05). Bland-Altman analysis showed good agreement between PWD-CO and MD-CO in the general population, the median bias was 0.02 L/min, the limits of agreement were -1.92 to +1.92 L/min. The agreement was better in patients with LVEF less than 60% with a median bias of 0.005 L/min and limits of agreement of -1.56 to 1.55 L/min. The percentage error was 17% in both cases. Conclusion: Measurement of MD in critically ill patients provides a simple and accurate estimate of CO, especially in patients with reduced or preserved LVEF. This would allow earlier cardiovascular assessment in patients with circulatory failure, which is of particular interest in difficult clinical or technical conditions.

Effectiveness of prolonged versus standard-course of oseltamivir in critically ill patients with severe influenza infection: A multicentre cohort study.

The aim of this study is to investigate the effectiveness of prolonged versus standard course oseltamivir treatment among critically ill patients with severe influenza. A retrospective study of a prospectively collected database including adults with influenza infection admitted to 184 intensive care units (ICUs) in Spain from 2009 to 2018. Prolonged oseltamivir was defined if patients received the treatment beyond 5 days, whereas the standard-course group received oseltamivir for 5 days. The primary outcome was all-cause ICU mortality. Propensity score matching (PSM) was constructed, and the outcome was investigated through Cox regression and RCSs. Two thousand three hundred and ninety-seven subjects were included, of whom 1943 (81.1%) received prolonged oseltamivir and 454 (18.9%) received standard treatment. An optimal full matching algorithm was performed by matching 2171 patients, 1750 treated in the prolonged oseltamivir group and 421 controls in the standard oseltamivir group. After PSM, 387 (22.1%) patients in the prolonged oseltamivir and 119 (28.3%) patients in the standard group died (p = 0.009). After adjusting confounding factors, prolonged oseltamivir significantly reduced ICU mortality (odds ratio [OR]: 0.53, 95% confidence interval [CI]: 0.40-0.69). Prolonged oseltamivir may have protective effects on survival at Day 10 compared with a standard treatment course. Sensitivity analysis confirmed these findings. Compared with standard treatment, prolonged oseltamivir was associated with reduced ICU mortality in critically ill patients with severe influenza. Clinicians should consider extending the oseltamivir treatment duration to 10 days, particularly in higher-risk groups of prolonged viral shedding. Further randomized controlled trials are warranted to confirm these findings.

Timing of intubation and ICU mortality in COVID-19 patients: a retrospective analysis of 4198 critically ill patients during the first and second waves.

BACKGROUND: The optimal time to intubate patients with SARS-CoV-2 pneumonia has not been adequately determined. While the use of non-invasive respiratory support before invasive mechanical ventilation might cause patient-self-induced lung injury and worsen the prognosis, non-invasive ventilation (NIV) is frequently used to avoid intubation of patients with acute respiratory failure (ARF). We hypothesized that delayed intubation is associated with a high risk of mortality in COVID-19 patients. METHODS: This is a secondary analysis of prospectively collected data from adult patients with ARF due to COVID-19 admitted to 73 intensive care units (ICUs) between February 2020 and March 2021. Intubation was classified according to the timing of intubation. To assess the relationship between early versus late intubation and mortality, we excluded patients with ICU length of stay (LOS) < 7 days to avoid the immortal time bias and we did a propensity score and a cox regression analysis. RESULTS: We included 4,198 patients [median age, 63 (54‒71) years; 71% male; median SOFA (Sequential Organ Failure Assessment) score, 4 (3‒7); median APACHE (Acute Physiology and Chronic Health Evaluation) score, 13 (10‒18)], and median PaO2/FiO2 (arterial oxygen pressure/ inspired oxygen fraction), 131 (100‒190)]; intubation was considered very early in 2024 (48%) patients, early in 928 (22%), and late in 441 (10%). ICU mortality was 30% and median ICU stay was 14 (7‒28) days. Mortality was higher in the "late group" than in the "early group" (37 vs. 32%, p < 0.05). The implementation of an early intubation approach was found to be an independent protective risk factor for mortality (HR 0.6; 95%CI 0.5‒0.7). CONCLUSIONS: Early intubation within the first 24 h of ICU admission in patients with COVID-19 pneumonia was found to be an independent protective risk factor of mortality. TRIAL REGISTRATION: The study was registered at Clinical-Trials.gov (NCT04948242) (01/07/2021).

Risk factors for developing ventilator-associated lower respiratory tract infection in patients with severe COVID-19: a multinational, multicentre study, prospective, observational study.

Around one-third of patients diagnosed with COVID-19 develop a severe illness that requires admission to the Intensive Care Unit (ICU). In clinical practice, clinicians have learned that patients admitted to the ICU due to severe COVID-19 frequently develop ventilator-associated lower respiratory tract infections (VA-LRTI). This study aims to describe the clinical characteristics, the factors associated with VA-LRTI, and its impact on clinical outcomes in patients with severe COVID-19. This was a multicentre, observational cohort study conducted in ten countries in Latin America and Europe. We included patients with confirmed rtPCR for SARS-CoV-2 requiring ICU admission and endotracheal intubation. Only patients with a microbiological and clinical diagnosis of VA-LRTI were included. Multivariate Logistic regression analyses and Random Forest were conducted to determine the risk factors for VA-LRTI and its clinical impact in patients with severe COVID-19. In our study cohort of 3287 patients, VA-LRTI was diagnosed in 28.8% [948/3287]. The cumulative incidence of ventilator-associated pneumonia (VAP) was 18.6% [610/3287], followed by ventilator-associated tracheobronchitis (VAT) 10.3% [338/3287]. A total of 1252 bacteria species were isolated. The most frequently isolated pathogens were Pseudomonas aeruginosa (21.2% [266/1252]), followed by Klebsiella pneumoniae (19.1% [239/1252]) and Staphylococcus aureus (15.5% [194/1,252]). The factors independently associated with the development of VA-LRTI were prolonged stay under invasive mechanical ventilation, AKI during ICU stay, and the number of comorbidities. Regarding the clinical impact of VA-LRTI, patients with VAP had an increased risk of hospital mortality (OR [95% CI] of 1.81 [1.40-2.34]), while VAT was not associated with increased hospital mortality (OR [95% CI] of 1.34 [0.98-1.83]). VA-LRTI, often with difficult-to-treat bacteria, is frequent in patients admitted to the ICU due to severe COVID-19 and is associated with worse clinical outcomes, including higher mortality. Identifying risk factors for VA-LRTI might allow the early patient diagnosis to improve clinical outcomes.Trial registration: This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.

The Role of Biomarkers in Influenza and COVID-19 Community-Acquired Pneumonia in Adults.

Pneumonia is a growing problem worldwide and remains an important cause of morbidity, hospitalizations, intensive care unit admission and mortality. Viruses are the causative agents in almost a fourth of cases of community-acquired pneumonia (CAP) in adults, with an important representation of influenza virus and SARS-CoV-2 pneumonia. Moreover, mixed viral and bacterial pneumonia is common and a risk factor for severity of disease. It is critical for clinicians the early identification of the pathogen causing infection to avoid inappropriate antibiotics, as well as to predict clinical outcomes. It has been extensively reported that biomarkers could be useful for these purposes. This review describe current evidence and provide recommendations about the use of biomarkers in influenza and SARS-CoV-2 pneumonia, focusing mainly on procalcitonin (PCT) and C-reactive protein (CRP). Evidence was based on a qualitative analysis of the available scientific literature (meta-analyses, randomized controlled trials, observational studies and clinical guidelines). Both PCT and CRP levels provide valuable information about the prognosis of influenza and SARS-CoV-2 pneumonia. Additionally, PCT levels, considered along with other clinical, radiological and laboratory data, are useful for early diagnosis of mixed viral and bacterial CAP, allowing the proper management of the disease and adequate antibiotics prescription. The authors propose a practical PCT algorithm for clinical decision-making to guide antibiotic initiation in cases of influenza and SARS-CoV-2 pneumonia. Further well-design studies are needed to validate PCT algorithm among these patients and to confirm whether other biomarkers are indeed useful as diagnostic or prognostic tools in viral pneumonia.

Psychological symptoms in difficult-to-sedate critical care survivors.

BACKGROUND: Critical care survivors often experience symptoms of anxiety, depression, or post-traumatic stress disorder (PTSD). AIMS: To determine the prevalence and severity of psychological symptoms during the first 6 months after discharge from the intensive care unit (ICU) and to evaluate its association with patients who are difficult to sedate during admission. DESIGN: Descriptive, prospective analysis of psychological symptoms in survivors from medicosurgical ICU over a 2-year period. METHODS: All ICU survivors who required mechanical ventilation (MV) for more than 24 hours were followed for 6 months after their ICU discharge. ICU outcome and complications as well as the presence of psychological symptoms, 1 to 3 to 6 months after discharge were prospectively evaluated through phone interviews comparing the incidence and intensity of patients who were difficult to sedate during their ICU stay with those who were not. Descriptive analysis and multivariate logistic regression were performed. RESULTS: Data were obtained for 195 patients, of whom 30% experienced difficult sedation (DS). Difficult-to-sedate patients were younger (P = .001), less critically ill (APACHE II score P = .002), and more likely to engage in harmful use of alcohol (P = .001) and psychoactive/psychotropic drug abuse. They also spent longer times on MV and in the ICU (P = .001). Anxiety incidence at 1 to 3 to 6 months post-discharge was significantly higher in DS patients than in those who were not (87.7% vs 45.4%, 75.5% vs 29.0%, and 70.8% vs 23.7%; P < .01), respectively. Depression incidence was also significantly higher in the DS group (82.4% vs 43.1%, 66% vs 33.9%, and 60.4% vs 27.2%; [P = .001]) at 1 to 3 to 6 months, respectively. A higher percentage of patients in the DS group reported symptoms of PTSD at 1 month (28.1% vs 11.5%) (P = .007) when compared with non-DS group. CONCLUSIONS: Critical care survivors who are difficult to sedate during their ICU stay are more likely to present psychological sequelae. Early identification of at-risk patients is necessary to implement appropriate preventive strategies. RELEVANCE TO CLINICAL PRACTICE: Patients who are difficult to sedate in the ICU may develop psychological disorders upon discharge, which may negatively affect their recovery. The prevention of DS and the early detection of psychological disorders are essential to minimize its subsequent impact.

Impact of one year of pandemic on Spanish Intensive Care Units / Impacto de un año de pandemia en las Unidades de Cuidados Intensivos de España

Objective. To measure the impact of the pandemic inSpanish ICUs.Material and methods. On-line survey, conducted inApril 2021, among SEMICYUC members. Participants wereasked about number of patients admitted, increase in thenumber of beds and staff, structures created in the hospitaland self-assessment of the work performed.Results. We received 246 answers from 157 hospitals.67.7% of the ICUs were expanded during the pandemic, overall increase in beds of 58.6%. The ICU medical staff increasedby 6.1% and there has been a nursing shortage in 93.7% ofunits. Patients exceeded 200% the pre-pandemic ICU capacity.In 88% of the hospitals the collaboration of other specialistswas necessary. The predominant collaboration model consisted of the intensive care medicine specialist being responsiblefor triage and coordinating patient management. Despite that53.2% centres offered training for critical care, a deteriorationin the quality of care was perceived. 84.2% hospitals drew upa Contingency Plan and in 77.8% of the hospitals a multidisciplinary committee was set up to agree on decision-making.Self-evaluation of the work performed was outstandingand 91.9% felt proud of what they had achieved, however, upto 15% considered leaving their job.Conclusions. The Spanish ICUs assumed an unprecedented increase in the number of patients. They achieved it withouthardly increasing their staff and, while intensive care medicinetraining was carried out for other specialists who collaborated.The degree of job satisfaction was consistent with pre-pandemic levels. (AU)

Objetivo. Medir el impacto de la pandemia COVID-19 en las UCI españolas. Material y métodos. Cuestionario online, realizado en abril 2021 entre socios de SEMICYUC. Se interrogó acerca delnúmero de pacientes ingresados, incremento en número decamas y personal, estructuras creadas en el hospital y autoevaluación del trabajo realizado.Resultados. Recibimos 246 respuestas de 157 hospitales. El 67.7% de las UCI se expandieron durante la pandemia,con un incremento de camas del 58.6%. El personal médicode las UCI aumentó un 6.1% y hubo escasez de enfermería enel 93.7% de las unidades. Los pacientes excedieron un 200%la capacidad pre-pandemia y en el 88% de los hospitales fuenecesaria la colaboración de otros especialistas, siendo elmodelo predominante aquel en que el especialista en medicina intensiva era responsable del triaje y coordinaba el tratamiento del paciente. A pesar de que en el 53.2% de los centros se ofreció formación en medicina intensiva se detectó undeterioro de la calidad asistencial. El 84.2% de los hospitaleselaboraron un plan de contingencia y el 77.8% conformaronun comité multidisciplinar para consensuar decisiones. Laevaluación del trabajo fue sobresaliente y el 91.9% se sienteorgulloso del resultado, pero hasta el 15% consideró abandonar la especialidad.Conclusiones. Las UCI españolas asumieron un incremento de pacientes sin precedentes, sin apenas aumento delpersonal y mientras formaban a otros especialistas que colaboraron. El grado de satisfacción con el trabajo realizado fuesimilar al pre-pandemia. (AU)

Negative predictive value of procalcitonin to rule out bacterial respiratory co-infection in critical covid-19 patients.

BACKGROUND: Procalcitonin (PCT) and C-Reactive Protein (CRP) are useful biomarkers to differentiate bacterial from viral or fungal infections, although the association between them and co-infection or mortality in COVID-19 remains unclear. METHODS: The study represents a retrospective cohort study of patients admitted for COVID-19 pneumonia to 84 ICUs from ten countries between (March 2020-January 2021). Primary outcome was to determine whether PCT or CRP at admission could predict community-acquired bacterial respiratory co-infection (BC) and its added clinical value by determining the best discriminating cut-off values. Secondary outcome was to investigate its association with mortality. To evaluate the main outcome, a binary logistic regression was performed. The area under the curve evaluated diagnostic performance for BC prediction. RESULTS: 4635 patients were included, 7.6% fulfilled BC diagnosis. PCT (0.25[IQR 0.1-0.7] versus 0.20[IQR 0.1-0.5]ng/mL, p<0.001) and CRP (14.8[IQR 8.2-23.8] versus 13.3 [7-21.7]mg/dL, p=0.01) were higher in BC group. Neither PCT nor CRP were independently associated with BC and both had a poor ability to predict BC (AUC for PCT 0.56, for CRP 0.54). Baseline values of PCT<0.3ng/mL, could be helpful to rule out BC (negative predictive value 91.1%) and PCT≥0.50ng/mL was associated with ICU mortality (OR 1.5,p<0.001). CONCLUSIONS: These biomarkers at ICU admission led to a poor ability to predict BC among patients with COVID-19 pneumonia. Baseline values of PCT<0.3ng/mL may be useful to rule out BC, providing clinicians a valuable tool to guide antibiotic stewardship and allowing the unjustified overuse of antibiotics observed during the pandemic, additionally PCT≥0.50ng/mL might predict worsening outcomes.

Non-invasive oxygenation support in acutely hypoxemic COVID-19 patients admitted to the ICU: a multicenter observational retrospective study.

BACKGROUND: Non-invasive oxygenation strategies have a prominent role in the treatment of acute hypoxemic respiratory failure during the coronavirus disease 2019 (COVID-19). While the efficacy of these therapies has been studied in hospitalized patients with COVID-19, the clinical outcomes associated with oxygen masks, high-flow oxygen therapy by nasal cannula and non-invasive mechanical ventilation in critically ill intensive care unit (ICU) patients remain unclear. METHODS: In this retrospective study, we used the best of nine covariate balancing algorithms on all baseline covariates in critically ill COVID-19 patients supported with > 10 L of supplemental oxygen at one of the 26 participating ICUs in Catalonia, Spain, between March 14 and April 15, 2020. RESULTS: Of the 1093 non-invasively oxygenated patients at ICU admission treated with one of the three stand-alone non-invasive oxygenation strategies, 897 (82%) required endotracheal intubation and 310 (28%) died during the ICU stay. High-flow oxygen therapy by nasal cannula (n = 439) and non-invasive mechanical ventilation (n = 101) were associated with a lower rate of endotracheal intubation (70% and 88%, respectively) than oxygen masks (n = 553 and 91% intubated), p < 0.001. Compared to oxygen masks, high-flow oxygen therapy by nasal cannula was associated with lower ICU mortality (hazard ratio 0.75 [95% CI 0.58-0.98), and the hazard ratio for ICU mortality was 1.21 [95% CI 0.80-1.83] for non-invasive mechanical ventilation. CONCLUSION: In critically ill COVID-19 ICU patients and, in the absence of conclusive data, high-flow oxygen therapy by nasal cannula may be the approach of choice as the primary non-invasive oxygenation support strategy.

Dexamethasone as risk-factor for ICU-acquired respiratory tract infections in severe COVID-19.

PURPOSE: Dexamethasone is the only drug that has consistently reduced mortality in patients with COVID-19, especially in patients needing oxygen or invasive mechanical ventilation. However, there is a growing concern about the relation of dexamethasone with the unprecedented rates of ICU-acquired respiratory tract infections (ICU-RTI) observed in patients with severe COVID-19. METHODS: This was a multicenter, prospective cohort study; conducted in ten countries in Latin America and Europe. We included patients older than 18 with confirmed SARS-CoV-2 requiring ICU admission. A multivariate logistic regression and propensity score matching (PSM) analysis was conducted to determine the relation between dexamethasone treatment and ICU-RTI. RESULTS: A total of 3777 patients were included. 2065 (54.7%) were treated with dexamethasone within the first 24 h of admission. After performing the PSM, patients treated with dexamethasone showed significantly higher proportions of VAP (282/1652 [17.1%] Vs. 218/1652 [13.2%], p = 0.014). Also, dexamethasone treatment was identified as an adjusted risk factor of ICU-RTI in the multivariate logistic regression model (OR 1.64; 95%CI: 1.37-1.97; p < 0.001). CONCLUSION: Patients treated with dexamethasone for severe COVID-19 had a higher risk of developing ICU-acquired respiratory tract infections after adjusting for days of invasive mechanical ventilation and ICU length of stay, suggesting a cautious use of this treatment.

Impact of difficult sedation on the management and outcome of critically ill patients.

BACKGROUND: The term "difficult sedation" (DS) refers to situations of therapeutic failure, tolerance, or deprivation of the sedatives administered. AIMS: To characterize the profile of patients who developed DS and to assess its impact on the duration of mechanical ventilation (MV) and intensive care unit length of stay (ICU-LOS), as well as other complications related to their stay. DESIGN: A prospective descriptive analysis was conducted of the practices of analgesia/sedation in a medical-surgical intensive care unit (ICU) over a 2-year period. METHODS: All critically ill patients undergoing MV and sedation for more than 24 hours were prospectively followed until death or discharge. Demographic data, type, duration, complications of analgesia/sedation, and clinical outcome during ICU stay were recorded. Patients who developed DS were compared with those who were not difficult to sedate (not-DS). RESULTS: A total of 327 patients were included, 24.1% of whom were difficult to sedate (DS). Patients in the DS group were younger (P = .001); less severely ill (P = .003); and were more likely to have a history of smoking (P = .045), alcohol (P < .001), and psychotropic use (P = .001) than the not-DS group. Patients included in the DS group were sedated for longer periods (P < .001) and required higher doses of midazolam (P < .036), propofol (P = .023), and remifentanyl (P = .026) than those in the not-DS group. Difficult-to-sedate patients were twice as likely to require more than one sedative simultaneously (P < .001), presented more periods of over-sedation (P = .031)/under-sedation (P = .024), and suffered more pain (P < .001) than patients in the not-DS group. Patients in the DS group had prolonged MV times (P < .001), developed more pressure ulcers (P > .001) and ventilator-associated pneumonias (P = .025), and were more likely to require tracheotomy (P = .001) than those in the not-DS group. CONCLUSION: DS develops in one of four critically ill patients and has a negative impact on their outcomes. Early identification of the clinical profile of this group and active prevention and treatment are essential strategies in order to minimize its impact. RELEVANCE TO CLINICAL PRACTICE: A quarter of mechanically ventilated patients may develop situations of DS, which negatively affects their outcome. Early detection and prevention of DS are essential to minimize its impact.

Mortality comparison between the first and second/third waves among 3,795 critical COVID-19 patients with pneumonia admitted to the ICU: A multicentre retrospective cohort study.

BACKGROUND: It is unclear whether the changes in critical care throughout the pandemic have improved the outcomes in coronavirus disease 2019 (COVID-19) patients admitted to the intensive care units (ICUs). METHODS: We conducted a retrospective cohort study in adults with COVID-19 pneumonia admitted to 73 ICUs from Spain, Andorra and Ireland between February 2020 and March 2021. The first wave corresponded with the period from February 2020 to June 2020, whereas the second/third waves occurred from July 2020 to March 2021. The primary outcome was ICU mortality between study periods. Mortality predictors and differences in mortality between COVID-19 waves were identified using logistic regression. FINDINGS: As of March 2021, the participating ICUs had included 3795 COVID-19 pneumonia patients, 2479 (65·3%) and 1316 (34·7%) belonging to the first and second/third waves, respectively. Illness severity scores predicting mortality were lower in the second/third waves compared with the first wave according with the Acute Physiology and Chronic Health Evaluation system (median APACHE II score 12 [IQR 9-16] vs 14 [IQR 10-19]) and the organ failure assessment score (median SOFA 4 [3-6] vs 5 [3-7], p<0·001). The need of invasive mechanical ventilation was high (76·1%) during the whole study period. However, a significant increase in the use of high flow nasal cannula (48·7% vs 18·2%, p<0·001) was found in the second/third waves compared with the first surge. Significant changes on treatments prescribed were also observed, highlighting the remarkable increase on the use of corticosteroids to up to 95.9% in the second/third waves. A significant reduction on the use of tocilizumab was found during the study (first wave 28·9% vs second/third waves 6·2%, p<0·001), and a negligible administration of lopinavir/ritonavir, hydroxychloroquine, and interferon during the second/third waves compared with the first wave. Overall ICU mortality was 30·7% (n = 1166), without significant differences between study periods (first wave 31·7% vs second/third waves 28·8%, p = 0·06). No significant differences were found in ICU mortality between waves according to age subsets except for the subgroup of 61-75 years of age, in whom a reduced unadjusted ICU mortality was observed in the second/third waves (first 38·7% vs second/third 34·0%, p = 0·048). Non-survivors were older, with higher severity of the disease, had more comorbidities, and developed more complications. After adjusting for confounding factors through a multivariable analysis, no significant association was found between the COVID-19 waves and mortality (OR 0·81, 95% CI 0·64-1·03; p = 0·09). Ventilator-associated pneumonia rate increased significantly during the second/third waves and it was independently associated with ICU mortality (OR 1·48, 95% CI 1·19-1·85, p<0·001). Nevertheless, a significant reduction both in the ICU and hospital length of stay in survivors was observed during the second/third waves. INTERPRETATION: Despite substantial changes on supportive care and management, we did not find significant improvement on case-fatality rates among critical COVID-19 pneumonia patients. FUNDING: Ricardo Barri Casanovas Foundation (RBCF2020) and SEMICYUC.

Corticosteroid treatment and mortality in mechanically ventilated COVID-19-associated acute respiratory distress syndrome (ARDS) patients: a multicentre cohort study.

BACKGROUND: Some unanswered questions persist regarding the effectiveness of corticosteroids for severe coronavirus disease 2019 (COVID-19) patients. We aimed to assess the clinical effect of corticosteroids on intensive care unit (ICU) mortality among mechanically ventilated COVID-19-associated acute respiratory distress syndrome (ARDS) patients. METHODS: This was a retrospective study of prospectively collected data conducted in 70 ICUs (68 Spanish, one Andorran, one Irish), including mechanically ventilated COVID-19-associated ARDS patients admitted between February 6 and September 20, 2020. Individuals who received corticosteroids for refractory shock were excluded. Patients exposed to corticosteroids at admission were matched with patients without corticosteroids through propensity score matching. Primary outcome was all-cause ICU mortality. Secondary outcomes were to compare in-hospital mortality, ventilator-free days at 28 days, respiratory superinfection and length of stay between patients with corticosteroids and those without corticosteroids. We performed survival analysis accounting for competing risks and subgroup sensitivity analysis. RESULTS: We included 1835 mechanically ventilated COVID-19-associated ARDS, of whom 1117 (60.9%) received corticosteroids. After propensity score matching, ICU mortality did not differ between patients treated with corticosteroids and untreated patients (33.8% vs. 30.9%; p = 0.28). In survival analysis, corticosteroid treatment at ICU admission was associated with short-term survival benefit (HR 0.53; 95% CI 0.39-0.72), although beyond the 17th day of admission, this effect switched and there was an increased ICU mortality (long-term HR 1.68; 95% CI 1.16-2.45). The sensitivity analysis reinforced the results. Subgroups of age < 60 years, severe ARDS and corticosteroids plus tocilizumab could have greatest benefit from corticosteroids as short-term decreased ICU mortality without long-term negative effects were observed. Larger length of stay was observed with corticosteroids among non-survivors both in the ICU and in hospital. There were no significant differences for the remaining secondary outcomes. CONCLUSIONS: Our results suggest that corticosteroid treatment for mechanically ventilated COVID-19-associated ARDS had a biphasic time-dependent effect on ICU mortality. Specific subgroups showed clear effect on improving survival with corticosteroid use. Therefore, further research is required to identify treatment-responsive subgroups among the mechanically ventilated COVID-19-associated ARDS patients.

Understanding critically ill sepsis patients with normal serum lactate levels: results from U.S. and European ICU cohorts.

While serum lactate level is a predictor of poor clinical outcomes among critically ill patients with sepsis, many have normal serum lactate. A better understanding of this discordance may help differentiate sepsis phenotypes and offer clues to sepsis pathophysiology. Three intensive care unit datasets were utilized. Adult sepsis patients in the highest quartile of illness severity scores were identified. Logistic regression, random forests, and partial least square models were built for each data set. Features differentiating patients with normal/high serum lactate on day 1 were reported. To exclude that differences between the groups were due to potential confounding by pre-resuscitation hyperlactatemia, the analyses were repeated for day 2. Of 4861 patients included, 47% had normal lactate levels. Patients with normal serum lactate levels had lower 28-day mortality rates than those with high lactate levels (17% versus 40%) despite comparable physiologic phenotypes. While performance varied between datasets, logistic regression consistently performed best (area under the receiver operator curve 87-99%). The variables most strongly associated with normal serum lactate were serum bicarbonate, chloride, and pulmonary disease, while serum sodium, AST and liver disease were associated with high serum lactate. Future studies should confirm these findings and establish the underlying pathophysiological mechanisms, thus disentangling association and causation.

Prognostic Value of Procalcitonin and C-Reactive Protein in 1608 Critically Ill Patients with Severe Influenza Pneumonia.

Background: Procalcitonin (PCT) and C-Reactive protein (CRP) are well-established sepsis biomarkers. The association of baseline PCT levels and mortality in pneumonia remains unclear, and we still do not know whether biomarkers levels could be related to the causative microorganism (GPC, GNB). The objective of this study is to address these issues. Methods: a retrospective observational cohort study was conducted in 184 Spanish ICUs (2009-2018). Results: 1608 patients with severe influenza pneumonia with PCT and CRP available levels on admission were included, 1186 with primary viral pneumonia (PVP) and 422 with bacterial Co-infection (BC). Those with BC presented higher PCT levels (4.25 [0.6-19.5] versus 0.6 [0.2-2.3]ng/mL) and CRP (36.7 [20.23-118] versus 28.05 [13.3-109]mg/dL) as compared to PVP (p < 0.001). Deceased patients had higher PCT (ng/mL) when compared with survivors, in PVP (0.82 [0.3-2.8]) versus 0.53 [0.19-2.1], p = 0.001) and BC (6.9 [0.93-28.5] versus 3.8 [0.5-17.37], p = 0.039). However, no significant association with mortality was observed in the multivariate analysis. The PCT levels (ng/mL) were significantly higher in polymicrobial infection (8.4) and GPC (6.9) when compared with GNB (1.2) and Aspergillus (1.7). The AUC-ROC of PCT for GPC was 0.67 and 0.32 for GNB. The AUROC of CRP was 0.56 for GPC and 0.39 for GNB. Conclusions: a single PCT/CRP value at ICU admission was not associated with mortality in severe influenza pneumonia. None of the biomarkers have enough discriminatory power to be used for predicting the causative microorganism of the co-infection.